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Issue 3, 2010
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A systems perspective of host–pathogen interactions: predicting disease outcome in tuberculosis

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Abstract

The complex web of interactions between the host immune system and the pathogen determines the outcome of any infection. A computational model of this interaction network, which encodes complex interplay among host and bacterial components, forms a useful basis for improving the understanding of pathogenesis, in filling knowledge gaps and consequently to identify strategies to counter the disease. We have built an extensive model of the Mycobacterium tuberculosishost–pathogen interactome, consisting of 75 nodes corresponding to host and pathogen molecules, cells, cellular states or processes. Vaccination effects, clearance efficiencies due to drugs and growth rates have also been encoded in the model. The system is modelled as a Boolean network. Virtual deletion experiments, multiple parameter scans and analysis of the system’s response to perturbations, indicate that disabling processes such as phagocytosis and phagolysosome fusion or cytokines such as TNF-α and IFN-γ, greatly impaired bacterial clearance, while removing cytokines such as IL-10 alongside bacterial defence proteins such as SapM greatly favour clearance. Simulations indicate a high propensity of the pathogen to persist under different conditions.

Graphical abstract: A systems perspective of host–pathogen interactions: predicting disease outcome in tuberculosis

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Publication details

The article was received on 19 Jun 2009, accepted on 05 Oct 2009 and first published on 14 Dec 2009


Article type: Paper
DOI: 10.1039/B912129C
Citation: Mol. BioSyst., 2010,6, 516-530
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    A systems perspective of host–pathogen interactions: predicting disease outcome in tuberculosis

    K. Raman, A. G. Bhat and N. Chandra, Mol. BioSyst., 2010, 6, 516
    DOI: 10.1039/B912129C

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